| First Author | Jin J | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 7502 |
| PubMed ID | 28790310 | Mgi Jnum | J:275156 |
| Mgi Id | MGI:6296252 | Doi | 10.1038/s41598-017-06868-8 |
| Citation | Jin J, et al. (2017) P16 (INK4a) Deletion Ameliorated Renal Tubulointerstitial Injury in a Stress-induced Premature Senescence Model of Bmi-1 Deficiency. Sci Rep 7(1):7502 |
| abstractText | To determine whether p16 (INK4a) deletion ameliorated renal tubulointerstitial injury by inhibiting a senescence-associated secretory phenotype (SASP) in Bmi-1-deficient (Bmi-1 (-/-)) mice, renal phenotypes were compared among 5-week-old Bmi-1 and p16 (INK4a) double-knockout, and Bmi-1 (-/-) and wild-type mice. Fifth-passage renal interstitial fibroblasts (RIFs) from the three groups were analyzed for senescence and proliferation. The effect of Bmi-1 deficiency on epithelial-to-mesenchymal transition (EMT) was examined in Bmi-1-knockdown human renal proximal tubular epithelial (HK2) cells, which were treated with concentrated conditioned medium (CM) from the fifth-passage renal interstitial fibroblasts (RIFs) of above three group mice or with exogenous TGF-beta1. Our results demonstrated that p16 (INK4a) deletion largely rescued renal aging phenotypes caused by Bmi-1 deficiency, including impaired renal structure and function, decreased proliferation, increased apoptosis, senescence and SASP, DNA damage, NF-kappaB and TGF-beta1/Smad signal activation, inflammatory cell infiltration, and tubulointerstitial fibrosis and tubular atrophy. P16 (INK4a) deletion also promoted proliferation, reduced senescence and SASP of RIFs and subsequently inhibited EMT of Bmi-1-knockdown HK2 cells. TGF-beta1 further induced the EMT of Bmi-1-knockdown HK2 cells. Thus, p16 (INK4a) positive senescent cells would be a therapeutic target for preventing renal tubulointerstitial injury. |
